The immune response to foreign antigens is primarily mediated by T lymphocytes expressing an antigen-specific receptor complex including an alpha- and a beta-chain heterodimer associated with the polypeptides termed CD3. A second class of T cells has been identified that expresses a different gamma and delta-chain heterodimer associated with the CD3 polypeptides. The immune function and specificity of these T cells are presently unknown, although their presence in all mammalian and avian species thus far examined indicates that they have a fundamental role in immunity. In order to understand some of the basic developmental and functional characteristics o gamma/delta-bearing T cells a set of experiments is proposed to examine the maturation of gamma/delta-bearing T cells in transgenic mice. Recent work has resulted in the identification of gamma/delta-bearing T cell lines that have specificity for determinants on molecules encoded by genes linked to the major histocompatibility complex (MHC). These cells afford a way to examine the function of gamma/delta-bearing T cells in antigen-specific immune interactions. We have inserted the productively rearranged genes cloned from one such antigen-specific gamma/delta-bearing T cell clone into the germline of mice, and preliminary data indicate that the gamma delta T cell receptor is expressed on most or all of the T cells in the transgenic animals. We propose to examine the ontogeny, tissue-specificity, and immune function of cells bearing the transgenic gamma delta receptor. Particular emphasis will be placed on the processes of tolerance and selection that govern the development of gamma delta T cells. These experiments will provide information pertaining to the contribution of gamma/delta-bearing T cells to self-nonself discrimination and specific immunity.